Immunosuppressive Therapy in Duchenne Muscular Dystrophy: Considerations for Myoblast Transfer Studies

  • Jerry R. Mendell
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 280)


The issue of immunosuppressive therapy in relation to myoblast transfer is extremely important. Several points must be addressed. The first to consider is whether immunosuppression is necessary for this treatment to be successful. The second is the choice of drugs to be used and what impact they will have on the natural history of the disease exclusive of the potential benefits of the transplanted cells.


Duchenne Dystrophy Duchenne Muscular Dystrophy Mouse Mammary Tumor Virus Prednisone Group Side EFfECT 
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  1. 1.
    G. Karpati, Y. Pouliot, P. Holland, et al., Dystrophin is detected in mdx skeletal muscle fibers mosaicized by non-dystrophic myonuclei through the implantation of cultured myoblasts, Neurology 39 (Suppl. 1): 153–154, (1989).CrossRefGoogle Scholar
  2. 2.
    G. Karpati, Y. Pouliot, S. Carpenter, et al., Implantation of non-dystrophic allogenic myoblasts into dystrophic models of mdx mice produces “mosaic” fibers of normal microscopic phenotype, in: “Cell and Molec. Biol. of Muscle Devel.” L.H. Kedes, F.E. Stockdale, eds., A.R. Liss, 973–985 (1989).Google Scholar
  3. 3.
    G. Karpati, Y. Pouliot, S, Carpenter, Expression of immunoreactive major histocompatibility complex products in human skeletal muscles. Ann. Neurol. 23: 64–72 (1988).PubMedCrossRefGoogle Scholar
  4. 4.
    S. T. Appleyard, M. J. Dunn, V. Dubowitz, et al., Increased expression of HLA ABL class 1 antigens by muscle fibers in Duchenne muscular dystrophy, inflammatory myopathy and other neuromuscular disorders, Lancet. 2: 361363 (1985).CrossRefGoogle Scholar
  5. 5.
    D. A. Isenberg, D. Rowe, M. Shearer, et al., Localization of interferons and interleukin 2 in polymyositis and muscular dystrophy. Clin. Exp. Immunol. 63: 450–458 (1986).PubMedGoogle Scholar
  6. 6.
    J. A. Zuk, A. Fletcher, Skeletal muscle expression of class II histocompatibility antigens (HLA-DR) in polymyositis and other muscle disorders with an inflammatory infiltrate, J. Clin. Path. 41: 410–414 (1988).Google Scholar
  7. 7.
    T. A. Partridge, J. E. Morgan, G. R. Coulton, et al., Conversion of mdx myofibers from dystrophin-negative todystrophin-positive by injection of normal myoblasts, Nature 337: 176–179 (1989).Google Scholar
  8. 8.
    P. K. Law, T. G. Goodwin, M. G. Wang, Normal myoblast injections provide genetic treatment for murine dystrophy, Muscle and Nerve 11: 525–533 (1988).PubMedCrossRefGoogle Scholar
  9. 9.
    D. J. Watt, J. E. Morgan, T. A. Partridge, Long term survival of allografted muscle precursor cells following a limited period of treatment with cyclosporin A, Clin. Exp. Immunol. 55: 419–426 (1984).Google Scholar
  10. 10.
    P. K. Law, T. G. Goodwin, H-J. Lin, Histoincompatible myoblast injection improves muscle structure and function of dystrophic mice, Transplant Proc. Vol. XX: 1114–1119 (1988).Google Scholar
  11. 11.
    D. Fries, C. Hiesse, G. Santelli, et al., Triple therapy with low-dose cyclosporin, azathioprine, and steroids: long-term results of a randomized study in cadaver donor renal transplantation, Transplant Proc. Vol. XX: 130–135 (1988).Google Scholar
  12. 12.
    S. Caglar, I. Tasdemir, C. Turgan, et al., The effect of triple therapy on graft outcome in renal transplantation, Transplant Proc. Vol. XX: 140–142 (1988).Google Scholar
  13. 13.
    C. Hiesse, P. Prevost, M. Busson, et al., Triple-drug regimen (TDR) of AZA + CsA + P: New definition of factors influencing kidney graft survival at a single center, Transplant Proc. Vol. 21: 1646–1647 (1989).PubMedGoogle Scholar
  14. 14.
    M. I. Lorber, S. M. Flechner, C.T. Van Buren, et al., Cyclosporin, azathioprine, and prednisone as treatment for cyclosporin-induced nephrotoxicity in renal transplant recipients. Transplant Proc. 17: 282–284 (1985).PubMedGoogle Scholar
  15. 15.
    S. Kolkin, N. S. Nahman Jr., J. R. Mendell, Chronic nephrotoxicity complicating cyclosporin treatment of chronic inflammatory demyelinating polyradiculoneuropathy, Neurology 37: 147–149 (1987).PubMedCrossRefGoogle Scholar
  16. 16.
    S. A. Richard, M. D. Tindall, J. A. Rollins, et al., Preliminary results of a double-blind, randomized, placebo-controlled trial of cyclosporin in myasthenia gravis, N. Engl. J. Med. 316: 719–724 (1987).CrossRefGoogle Scholar
  17. 17.
    J. T. Kissel, R. J. Levy, J. R. Mendell, et al., Azathioprine toxicity in neuromuscular disease, Neurology 36: 35–39 (1986).PubMedCrossRefGoogle Scholar
  18. 18.
    D. B. Drachman, R. V. Toyka, E. Myer, Prednisone in Duchenne muscular dystrophy, Lancet. 2: 1409–1412 (1974).PubMedCrossRefGoogle Scholar
  19. 19.
    S. DeSilva, D. B. Drachman, D. Melitis, et al., Prednisone treatment in Duchenne muscular dystrophy: long-term benefit, Arch. Neurol. 44: 818–822 (1987).Google Scholar
  20. 20.
    M. H. Brooke, G. M. Fenichel, R. C. Griggs, et al., Clinical investigation of Duchenne dystrophy. Interesting results in a trial of prednisone, Arch. Neurol. 44: 812–818 (1987).PubMedCrossRefGoogle Scholar
  21. 21.
    J. R. Mendell, R. T. Moxley, R. C. Griggs, et al., Randomized, double-blind six-month trial of prednisone in Duchenne’s muscular dystrophy. N. Engl. J. Med. 320: 1592–1597 (1989).PubMedCrossRefGoogle Scholar
  22. 22.
    M. H. Brooke, G. M. Fenichel, R. C.Griggs, et al., Clinical investigation in Duchenne dystrophy: 2. Determination of the “power” of therapeutic trials based on the natural history, Muscle and Nerve 6: 91–103 (1983).PubMedCrossRefGoogle Scholar
  23. 23.
    G. M. Ringold, Steroid hormone regulation of gene expression, Ann. Rev. Pharmacol. Toxicol. 25: 529–566 (1985).CrossRefGoogle Scholar
  24. 24.
    G. M. Ringold, K. R. Yamamoto, J. M. Bishop, Glucocorticoid-stimulated accumulation of mouse mammary tumor virus RNA: increased rate of synthesis of viral RNA, Proc. Natl. Acad. Sci. 74: 2879–2883 (1977).PubMedCrossRefGoogle Scholar
  25. 25.
    H. A. Young, T. Y. Shih, E. M. Scolnick, et al., Steroid induction of mouse mammary tumor virus: effect upon synthesis and degradation of viral RNA. J. Virol. 21: 139146 (1977).Google Scholar
  26. 26.
    J. E. Parrillo, A. S. Fauci, Mechanisms of glucocorticoid action on immune processes. Ann. Rev. Pharmacol. Toxicol. 19: 179–201 (1979).Google Scholar
  27. 27.
    T. C. Cesario, L. Slater, W. J. Poo, et al., The effect of hydrocortisone on the production of gamma-interferon and other lymphokines by human peripheral blood mononuclear cells, J. Interferon Res. 6: 337–347 (1986).PubMedCrossRefGoogle Scholar
  28. 28.
    K. Arahata, A. G. Engel, Monoclonal antibody analysis of mononuclear cells in myopathies. I. Quantitation of subsets according to diagnosis and sites of accumulation and demonstration and counts of muscle fibers invaded by T cells, Ann. Neurol. 16: 193–208 (1984).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1990

Authors and Affiliations

  • Jerry R. Mendell
    • 1
  1. 1.Department of NeurologyOhio State UniversityColumbusUSA

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